The factors that prevent normal B lymphocyte differentiation in patients with various forms of primary and secondary immunodeficiency will be investigated, from two points of view: On the one hand, in vitro analysis will be done to investigate the nature of the defective B cell differentiation that has so far not been defined, but for want of better terminology currently seems "intrinsic" to the B lymphocytes. Patient B cells will be exposed to polyclonal B cell activators that directly stimulate normal B cells to divide and differentiate. On the other hand, clinical investigation of hypogammaglobulinemic patients whose immunopathologic mechanism has already been reasonably well defined by prior study will involve a search, through both in vivo and further in vitro experiments, to repair normal immunity function. This will be done by removing, pharmacologically or by physical means, suppresive influences on, or providing factors found necessary for B cell development. Such patients, unfortunately, represent so far a small minority of the group of individuals currently under investigation. Through an improved understanding and documentation of the variety of defects operating in the pathogenesis of these disorders, should come increased knowledge of the normal immunobiology of lymphoid cells in man.